Solid dose delivery vehicle and methods of making same

Abstract

The present invention encompasses a solid dose delivery vehicle for ballistic administration of a bioactive material to subcutaneous and intradermal tissue, the delivery vehicle being sized and shaped for penetrating the epidermis. The delivery vehicle further comprises a stabilizing polyol glass loaded with the bioactive material and capable of releasing the bioactive material in situ. The present invention further includes methods of making and using the solid dose delivery vehicle of the invention.

1. A therapeutic composition in solid dose form comprising a bioactive material and a carbohydrate, wherein
 a) the bioactive material is a protein, 
 b) the therapeutic composition is a powder comprising therapeutic particles having a particle size distribution suitable for pulmonary administration, 
 c) the therapeutic particles are in a glassy state, 
 d) the bioactive material and the carbohydrate are dispersed within the therapeutic particles of the powder, 
 e) the carbohydrate is selected from the group consisting of monosaccharides, disaccharides and sugar alcohols, 
 f) the therapeutic particles remain in the glassy state when stored at elevated temperature, wherein the elevated temperature is 60° C., 
 g) the protein is distributed homogeneously and in solid solution in the carbohydrate, and 
 h) the therapeutic particles have a mean particle size of 0.5 to 5 μm. 
 
     
     
       2. The therapeutic composition according to  claim 1 , the therapeutic particles further comprising a physiologically acceptable inhibitor of the Maillard reaction. 
     
     
       3. The therapeutic composition according to  claim 1 , the therapeutic particles further comprising a biodegradable glass. 
     
     
       4. The therapeutic composition according to  claim 1 , wherein the therapeutic particles have a mean particle size of 1 to 4 μm. 
     
     
       5. The therapeutic composition according to  claim 1 , wherein the carbohydrate is trehalose. 
     
     
       6. The therapeutic composition according to  claim 1 , wherein the protein is insulin. 
     
     
       7. The therapeutic composition according to  claim 6 , wherein the therapeutic particles have a mean particle size of 1 to 4 μm. 
     
     
       8. The therapeutic composition according to  claim 1 , wherein the protein is insulin and the carbohydrate is trehalose. 
     
     
       9. The therapeutic composition according to  claim 8 , wherein the therapeutic particles have a mean particle size of 1 to 4 μm. 
     
     
       10. The therapeutic composition according to  claim 1 , the therapeutic particles further comprising an amino acid that is capable of inhibiting the Maillard reaction. 
     
     
       11. The therapeutic composition according to  claim 1 , wherein the bioactive material is stabilized for storage at elevated temperature for one month. 
     
     
       12. The therapeutic composition according to  claim 1 , wherein the therapeutic composition is suitable for delivering the bioactive material by transalveolar administration. 
     
     
       13. A therapeutic composition in solid dose form comprising a bioactive material and a carbohydrate, wherein
 a) the bioactive material is a protein, 
 b) the therapeutic composition comprises therapeutic particles in a glassy state, 
 c) the therapeutic composition is a powder having a particle size distribution suitable for pulmonary administration, 
 d) the bioactive material and the carbohydrate are dispersed within the therapeutic particles of the powder, 
 e) the therapeutic particles further comprise a glass modifier, wherein the glass modifier is not the bioactive material, 
 f) the carbohydrate is selected from the group consisting of monosaccharides, disaccharides and sugar alcohols, 
 g) the therapeutic particles remain in the glassy state when stored at elevated temperature, wherein the elevated temperature is 60° C., 
 h) the protein is distributed homogeneously and in solid solution in the carbohydrate, and 
 i) the particles have a mean particle size of 0.5 to 5 μm. 
 
     
     
       14. The therapeutic composition according to  claim 13 , wherein the glass modifier is a protein. 
     
     
       15. The therapeutic composition according to  claim 13 , said therapeutic particles further comprising a physiologically acceptable inhibitor of the Maillard reaction. 
     
     
       16. The therapeutic composition according to  claim 13 , said therapeutic particles further comprising a biodegradable glass. 
     
     
       17. The therapeutic composition according to  claim 13 , wherein the therapeutic particles have a mean particle size of 1 to 4 μm. 
     
     
       18. The therapeutic composition according to  claim 13 , wherein the carbohydrate is a sugar alcohol. 
     
     
       19. The therapeutic composition according to  claim 13 , wherein the carbohydrate is trehalose. 
     
     
       20. The therapeutic composition according to  claim 13 , wherein the protein is insulin. 
     
     
       21. The therapeutic composition according to  claim 20 , wherein the therapeutic particles have a mean particle size of 1 to 4 μm. 
     
     
       22. The therapeutic composition according to  claim 13 , wherein the protein is insulin and the carbohydrate is trehalose. 
     
     
       23. The therapeutic composition according to  claim 22 , wherein the therapeutic particles have a mean particle size of 1 to 4 μm. 
     
     
       24. The therapeutic composition according to  claim 13 , said therapeutic particles further comprising an amino acid that is capable of inhibiting the Maillard reaction. 
     
     
       25. The therapeutic composition according to  claim 13 , wherein the bioactive material is stabilized for storage at elevated temperature for one month. 
     
     
       26. The therapeutic composition according to  claim 13 , wherein the therapeutic composition is suitable for delivering the bioactive material by transalveolar administration. 
     
     
       27. The therapeutic composition according to  claim 1 , wherein the protein is insulin and the carbohydrate is a sugar alcohol. 
     
     
       28. The therapeutic composition according to  claim 1  or  27 , wherein the therapeutic particles remain in a glassy state at 70° C. 
     
     
       29. The therapeutic composition according to  claim 28 , said therapeutic particles further comprising a glass modifier, wherein the glass modifier is not the bioactive material. 
     
     
       30. The therapeutic composition according to  claim 28 , said therapeutic particles further comprising an amino acid that is capable of inhibiting the Maillard reaction. 
     
     
       31. The therapeutic composition according to  claim 28 , said therapeutic particles further comprising a physiologically acceptable inhibitor of the Maillard reaction. 
     
     
       32. The therapeutic composition according to  claim 28 , wherein the composition is suitable for transalveolar administration. 
     
     
       33. The therapeutic composition according to  claim 1 , wherein the therapeutic particles remain in the glassy state when stored at elevated temperature for one month. 
     
     
       34. The therapeutic composition according to  claim 33 , said therapeutic particles further comprising a glass modifier, wherein the glass modifier is not the bioactive material. 
     
     
       35. The therapeutic composition according to  claim 33 , said therapeutic particles further comprising an amino acid that is capable of inhibiting the Maillard reaction. 
     
     
       36. The therapeutic composition according to  claim 33 , wherein the therapeutic particles remain in the glassy state at 70° C. 
     
     
       37. The therapeutic composition according to  claim 36 , said therapeutic particles further comprising a glass modifier, wherein the glass modifier is not the bioactive material. 
     
     
       38. The therapeutic composition according to  claim 36 , said therapeutic particles further comprising an amino acid that is capable of inhibiting the Maillard reaction. 
     
     
       39. The therapeutic composition according to  claim 1 , wherein the carbohydrate is a disaccharide. 
     
     
       40. The therapeutic composition according to  claim 1 , wherein the carbohydrate is a sugar alcohol. 
     
     
       41. The therapeutic composition according to  claim 39  or  40 , said therapeutic particles further comprising a glass modifier, wherein the glass modifier is not the bioactive material. 
     
     
       42. The therapeutic composition according to  claim 39  or  40 , said therapeutic particles further comprising an amino acid that is capable of inhibiting the Maillard reaction. 
     
     
       43. The therapeutic composition according to  claim 39  or  40 , wherein the therapeutic particles remain in the glassy state at 70° C. 
     
     
       44. The therapeutic composition according to  claim 39  or  40 , wherein the therapeutic particles remain in the glassy state when stored at elevated temperature for one month. 
     
     
       45. The therapeutic composition according to  claim 3 , wherein the biodegradable glass is a water soluble glass. 
     
     
       46. The therapeutic composition according to  claim 45 , wherein the protein is insulin. 
     
     
       47. The therapeutic composition according to  claim 45 , wherein the carbohydrate is a sugar alcohol. 
     
     
       48. The therapeutic composition according to  claim 45  or  46  or  47 , wherein the composition is suitable for transalveolar administration. 
     
     
       49. The therapeutic composition according to  claim 48 , wherein the therapeutic particles remain in the glassy state when stored at 60° C. for one month. 
     
     
       50. The therapeutic composition according to  claim 49 , said therapeutic particles further comprising a physiologically acceptable inhibitor of the Maillard reaction. 
     
     
       51. The therapeutic composition according to  claim 45  or  46  or  47 , wherein the therapeutic particles remain in the glassy state when stored at 60° C. for one month. 
     
     
       52. The therapeutic composition according to  claim 45  or  46  or  47 , said therapeutic particles further comprising a physiologically acceptable inhibitor of the Maillard reaction.